Mechanical and biochemical activation and control of skeletal stem cells for cartilage regeneration
AssigneeThe Board of Trustees of the Leland Stanford Junior University
InventorsMichael T. Longaker, Charles K.F Chan, Matthew Philip Murphy
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Abstract
Methods and compositions are provided for the regeneration of articular cartilage by activating skeletal stem cells with a combination of (i) mechanical and (ii) biochemical stimulus. The mechanical stimulus can be an acute local injury. The biochemical stimulus can be a combination of an effective dose of a BMP2 activating agent and a VEGF inhibitor.
Claims15
A method for regenerating human articular cartilage in a subject with diminished chondrogenesis, the method comprising:
- activating human skeletal stem cells with a combination of (i) a mechanical stimulus, and (ii) a biochemical stimulus,
- wherein the mechanical stimulus is a surgically performed microfracture procedure to bone tissue at a desired site for articular cartilage regeneration;
- and
- wherein the biochemical stimulus is a combination of an effective dose of human BMP2 protein and a VEGF inhibitor.
A method for regenerating human articular cartilage in an aged human, the method comprising:
- activating human skeletal stem cells with a combination of (i) a mechanical stimulus, and (ii) a biochemical stimulus,
- wherein the mechanical stimulus is a surgically performed microfracture procedure to bone tissue at a desired site for articular cartilage regeneration;
- wherein the biochemical stimulus is a combination of an effective dose of human BMP2 protein and a VEGF inhibitor, wherein human BMP2 protein is provided at a dose of from about 10 μg to 10 mg, and the VEGF inhibitor is provided at a dose of from about 0.1 μg to 50 mg;
- and
- wherein the biochemical stimulus is provided within 3 days of the mechanical stimulus.
A method for regenerating human articular cartilage in an individual with osteoarthritis, the method comprising:
- activating human skeletal stem cells with a combination of (i) a mechanical stimulus, and (ii) a biochemical stimulus,
- wherein the mechanical stimulus is a surgically performed microfracture procedure to bone tissue at a desired site for articular cartilage regeneration;
- wherein the biochemical stimulus is a combination of an effective dose of human BMP2 protein and a VEGF inhibitor, wherein the human BMP2 protein is provided at a dose of from about 10 μg to 10 mg, and the VEGF inhibitor is provided at a dose of from about 0.1 μg to 50 mg;
- and
- wherein the biochemical stimulus is provided within 3 days of the mechanical stimulus.
Dependencies are inferred from the claim text.